We seek to leverage the resources of a large national birth cohort to address essential, novel questions aimed at providing guidance to clinicians on the management of depression during pregnancy. Advances in our knowledge of the safety of selective serotonin reuptake inhibitors (SSRIs) during pregnancy is critical to population health. In the U.S., approximately 6% of pregnant women use SSRIs, amounting to over 200,000 births per year of exposed offspring. Since serotonin (5-HT) plays a key role in early brain development, manipulation of 5-HT levels during this period can have lasting behavioral consequences. In a large national birth cohort in Finland, followed to age 14, we demonstrated that maternal SSRI exposure is associated with an increased risk of offspring depression and other adverse psychiatric outcomes independent of maternal diagnosis. However, there are many significant gaps in our understanding of the long-term effects of maternal SSRIs and offspring psychiatric disorders. The study has several strengths including the well-characterized birth cohort, a large sample size, and the capacity to link maternal SSRI use to offspring psychiatric outcomes spanning more than 2 decades. The main aim of the present study is to address novel questions on maternal SSRI exposure and offspring psychiatric outcomes, including depressive and anxiety disorders, autism spectrum disorders, and attention deficit hyperactivity disorder. For this purpose, we will use a prospective birth cohort study design and investigate the incidence of psychiatric outcomes up to age 21 in offspring exposed and unexposed to SSRIs in utero and capitalize on registry linkages of comprehensive nationwide databases on maternal antidepressant use, offspring psychiatric outcomes, research assessments, and other relevant variables. These data can be acquired in virtually all Finnish residents, who are entitled to universal health insurance. Specifically, we shall: 1) examine whether the sharp rise in risk of depression previously observed among maternal SSRI-exposed offspring in early adolescence continues into older age groups; 2) assess, using a research-based interview, whether offspring depression related to prenatal SSRI exposure is more severe than in offspring of unexposed mothers; 3) disambiguate from maternal SSRI use the contributions of maternal illness severity, familial loading, and postnatal maternal psychopathology on offspring psychiatric outcomes; 4) address vulnerability factors for offspring outcomes following maternal SSRI exposure, including gestational timing of exposure, antidepressant characteristics, and offspring sex; and 5) evaluate whether neonatal complications from SSRI withdrawal mediates associations between SSRIs and offspring outcomes. The findings of this study, in concert with research from other groups, are expected to provide information?which is insufficient at present?to help clinicians and patients make more informed decisions on the use of SSRIs during pregnancy, potentially diminishing harmful consequences while also reducing likelihood of relapse.